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Investigation into the genotoxic impurity, 1-methyl-4-nitrosopiperazine, in rifampicin.
- Source :
-
Journal of pharmaceutical and biomedical analysis [J Pharm Biomed Anal] 2024 Sep 15; Vol. 248, pp. 116303. Date of Electronic Publication: 2024 Jun 09. - Publication Year :
- 2024
-
Abstract
- This study assessed the presence of the genotoxic impurity 1-methyl-4-nitrosopiperazine (MNP) in 27 batches of rifampicin capsules obtained from 11 manufacturers in China. While they were below the temporary limit of 5 ppm set by the US Food and Drug Administration, the observed levels (0.33-2.36 ppm) exceeded the acceptable threshold of 0.16 ppm. Building upon preliminary findings and degradation experiments, we concluded that MNP is a by-product of the oxidative degradation of rifampicin or is introduced via oxidation or nitrosation during the synthesis process involving 1-methyl-4-aminopiperazine. The pathways of MNP formation were confirmed in this study. Furthermore, we observed that the addition of antioxidants, sealed storage, and selection of dominant crystal forms can aid in controlling MNP levels.<br />Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024. Published by Elsevier B.V.)
Details
- Language :
- English
- ISSN :
- 1873-264X
- Volume :
- 248
- Database :
- MEDLINE
- Journal :
- Journal of pharmaceutical and biomedical analysis
- Publication Type :
- Academic Journal
- Accession number :
- 38878455
- Full Text :
- https://doi.org/10.1016/j.jpba.2024.116303